Options for pharmacoresistant epilepsy in children: when medications don't work.

Medications are often first-line treatment for epilepsy in children. A detailed review of antiepileptic drugs and their application in various epilepsy syndromes is provided in the article "Antiepileptic Drugs--A Review" by Sankaraneni and Lachhwani (this issue). Here, we will focus on nonmedicinal approaches-some fairly longstanding and described since Biblical times such as the ketogenic diet while others are relatively new such as neurostimulation. Yet, others such as cannabinoids have been utilized for centuries for their medicinal properties, but we are just learning the scientific basis behind their efficacy. Families are often interested in nonmedicinal avenues of treatment, and knowledge of these options can empower a pediatrician to help families make choices that have scientific validity.

Variable manifestations of familial hemiplegic migraine associated with reversible cerebral edema in children.

Three children with familial hemiplegic migraine presented with right-sided weakness, speech difficulty, altered mental status, and gait abnormalities. These persistent aura signs were accompanied by left-sided slowing and cerebral dysfunction, documented by electroencephalograms. Cranial magnetic resonance imaging revealed cortical edema restricted to the left cerebral hemisphere. Follow-up electroencephalogram and imaging studies produced normal results 1-4 months afterward. However, cognitive changes persisted. Genetic testing demonstrated variable results: one child manifested a CACNA1A mutation compatible with familial hemiplegic migraine type 1, whereas another demonstrated an ATP1A2 sequence alteration. No known mutations were evident in the third child, with minor head trauma thought to precipitate the familial hemiplegic migraine. These findings demonstrate the variable clinical and genetic heterogeneity of childhood familial hemiplegic migraine.

Nerve root enhancement on spinal MRI in pediatric Guillain-Barré syndrome.

Guillain-Barré syndrome diagnosis is based on clinical presentation and supportive diagnostic testing. In its early stage, no single, reliable diagnostic test is available. However, a finding of nerve root enhancement on spinal magnetic resonance imaging may be useful. We evaluated the frequency of nerve root enhancement on spinal magnetic resonance imaging in children with Guillain-Barré syndrome. At a single tertiary pediatric center, we conducted a retrospective chart review of children with Guillain-Barré syndrome who had complete spinal or lumbosacral spinal magnetic resonance imaging with gadolinium administration from January 2002-January 2009. Twenty-four consecutive patients were identified. Spinal nerve root enhancement with gadolinium was present in 92% (22/24) of children with Guillain-Barré syndrome on initial spinal magnetic resonance imaging (95% confidence interval, 0.745-0.978). This finding increased to 100% of patients, after two patients underwent repeat spinal magnetic resonance imaging that did reveal nerve root enhancement. Patterns of enhancement were variable, but involved the thoracolumbar nerve roots in all patients. Enhancement of nerve roots with gadolinium on initial spinal magnetic resonance imaging was frequently present in these children with Guillain-Barré syndrome. Spinal magnetic resonance imaging is a sensitive diagnostic test and should be considered an additional diagnostic tool in select cases.

Disparities in hospital outcomes for injured people with epilepsy/seizures.

PURPOSE: Controlling for injury and patient characteristics, one would expect comparable in-hospital outcomes for injured patients with and without epilepsy. The historical stigma associated with epilepsy is well-documented, yet potential disparities in injury care for people with epilepsy/seizures have not been examined. We compared in-hospital outcomes of injured patients with epilepsy/seizures with patients without epilepsy/seizures and tested the hypothesis that injured people with epilepsy have worse outcomes. METHODS: Existing data were analyzed from the Nationwide Inpatient Sample-the largest, longitudinal, all-payer inpatient care database in the United States. Injured patients of all ages were included. Multivariable logistic regression was used to control for patient and hospital characteristics. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: When controlling for patient and injury characteristics, our results show that people with epilepsy/seizures were more likely to die in-hospital than people without epilepsy [odds ratio (OR) 1.17, p < 0.001]. People with epilepsy were significantly more likely to have a traumatic brain injury diagnosis than similar individuals without epilepsy (unintentional injuries OR 2.81, p < 0.001; interpersonal violence OR 6.0, p < 0.001). By mechanism of injury, significantly increased risk of death was observed for injuries from falls (OR 1.21, p < 0.001), other transport injuries (OR 2.04, p = 0.01), struck by/against (OR 1.85, p = 0.02), and suffocation (OR 10.93, p = 0.009). People with epilepsy/seizures receiving firearm injuries were less likely to die in-hospital (OR 0.25, p < 0.001). DISCUSSION: Disparities in hospital outcomes for people with epilepsy deserve further attention. Identifying the underlying causes of these disparities will allow for the development of targeted prevention interventions.

Disparities in injury death location for people with epilepsy/seizures.

OBJECTIVE: Wide variation has been reported in the proportion of injury deaths occurring during the prehospital phase. Potential disparities in where injured people with epilepsy and seizure disorders die have not been examined. We compared location of death between injured patients with epilepsy and seizure disorders and similar patients without epilepsy/seizures and tested the hypothesis that injured people with epilepsy/seizures are more likely to die outside of a hospital or health care setting. METHODS: U.S. vital statistics (mortality) data from the multiple cause of death files of the National Center for Health Statistics were analyzed. Patients less than 65 years of age at death who had injury as the underlying cause of death were included. Multinomial logistic regression was used to assess location of death, controlling for patient and injury characteristics. RESULTS: Controlling for potential confounders, people with epilepsy/seizures were more likely to die at home from unintentional injuries (relative risk ratio [RRR]=1.51, P<0.001) and less likely to die in public places (RRR=0.27, P<0.001). People with epilepsy/seizures were less likely to die at home or in public places from suicide, but significantly more likely to die at home from homicide (RRR=2.29, P<0.001). By mechanism of injury, people with epilepsy/seizures were more likely to die at home from drowning (RRR=2.35, P<0.001). DISCUSSION: Disparities in where injured people with epilepsy/seizures die deserve further attention. Identifying the underlying causes of these disparities will allow for the development of targeted prevention interventions.

Levetiracetam in the treatment of Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome is an epileptic encephalopathy characterized by multiple seizure types, mental retardation, and a slow spike-and-wave pattern on electroencephalography. Medical intractability is common. We identified a case series of six patients diagnosed with Lennox-Gastaut syndrome in which levetiracetam was initiated as add-on therapy for the management of seizures. At follow-up, four patients experienced 100% reduction of their myoclonic seizures; two patients had greater than 50% reduction of their atonic seizures, and four patients experienced 100% reduction in their generalized tonic-clonic seizures. Tonic seizures were not responsive to treatment. The most common side effect was irritability; the most positive change involved alertness. In this small sample, levetiracetam appeared effective in reducing seizures in Lennox-Gastaut syndrome. This preliminary study is limited by its retrospective design and small number of patients, but positive findings warrant a larger scale, multicenter study.

Anxiety in children with epilepsy.

Although the prevalence is unknown, affective disorders are more common in children with epilepsy than in healthy controls. The purpose of the present study was to examine the occurrence of anxiety in children and adolescents with epilepsy and to determine factors associated with elevation of these symptoms. Children and adolescents (n=101) between the ages of 6 and 16 years were given the Revised Children's Manifest Anxiety Scale (RCMAS). Mild to moderate symptoms of anxiety were reported by 23% of the patients. Based on regression analysis, factors significantly associated with increased anxiety included the presence of comorbid learning or behavioral difficulties, ethnicity, and polytherapy. Results suggest the need to monitor children and adolescents with epilepsy for affective symptoms in order to provide appropriate interventions.

Parental anxiety and quality of life in children with epilepsy.

Parental beliefs and attitudes concerning epilepsy may significantly impact adjustment and quality of life for both the child and family. The purpose of the present study was to examine the relationship between parental anxiety and quality of life in pediatric patients with ongoing epilepsy. Subjects were parents (n=200) of children between the ages of 6 and 16 years who had been diagnosed and treated for epilepsy for at least 1 year. Parents were given quality of life and anxiety questionnaires during the child's clinic visit. A stepwise regression analysis suggested that severity of comorbid conditions, parental anxiety, seizure control, and number of medications were significantly associated with quality of life for these children. Parents with increased anxiety whose children had poorly controlled seizures and a comorbid disability were found to have diminished quality of life.

The course of inattentive and hyperactive-impulsive symptoms in children with new onset seizures.

The purpose of the present study was to determine the prevalence of inattentive and hyperactive-impulsive symptoms in children with newly diagnosed epilepsy, explore the course of these symptoms over time, and examine factors associated with change in these symptoms. Parents of children (n=42) were administered the Attention Deficit Disorder Evaluation Scale-Home Version (ADDES-HV) at the time of diagnosis. The ADDES-HV was readministered after the child's seizures were controlled. Prior to initiation of anticonvulsant therapy, 31% of the children were rated as having clinically significant problems with inattention and 31% with hyperactivity-impulsivity. At follow-up, 27% had elevated symptoms of inattention and 24% had hyperactivity-impulsivity. Analysis of this change indicated that children with a normal MRI were more likely to have decreased hyperactive-impulsive behaviors following control of their seizures. Results suggest the need for assessment and monitoring of attention in children with epilepsy.

Symptom differences in children with absence seizures versus inattention.

Objective. Differentiation between the diagnoses of absence seizures and Attention Deficit Hyperactivity Disorder (ADHD), Predominantly Inattentive Type, is frequently confounded by similarities in symptom presentation. The purpose of the present study was to determine symptoms that would distinguish between the disorders.Methods. Prior to diagnosis, parents of children with absence seizures (n=17) or ADHD, Predominantly Inattentive Type (n=26), were administered the Attention Deficit Disorder Evaluation Scale-Home Version (ADDES-HV). A statistical model was developed based on age, gender, race, and items from the Inattentive Scale of the ADDES-HV.Results. Two items, "does not complete homework" and "does not remain on task," correctly classified 40 of 43 children. Children with absence seizures were rated by their parents as having a low rate of occurrence of these behaviors.Conclusion. Lack of sustained attention distinguished between the groups and was much more prevalent in children with ADHD, Predominantly Inattentive Type.

Factors Associated with Academic Achievement in Children with Controlled Epilepsy.

Children with epilepsy are at risk for academic underachievement. Multiple etiologies for this academic vulnerability have been suggested by past research including lower self-esteem, inattention, memory inefficiency, and lower socioeconomic status. The present study assessed 65 children (mean age = 10 years, 5 months) with well-controlled epilepsy on the four primary factors, as well as academic achievement and intelligence. A stepwise regression analysis was employed with academic achievement as the dependent variable and measures of self-esteem, attention, memory, and socioeconomic status as independent variables. When intelligence was controlled, attention was the only variable associated with achievement scores. Seizure variables including seizure type and duration of epilepsy were not associated with differences in academic performance. Findings support the importance of measuring attention skills in children with epilepsy and suggest that reduced auditory attention skills may be associated with decreased academic performance in these children.